Hydrochloric Acid → Roblitinib

HRID 1778093Notes

Reaction equation

HRID 1778093 reaction equation
Cl.[C:2]([C:4]1[C:5]([NH:37][CH2:38][CH2:39][O:40][CH3:41])=[CH:6][C:7]([NH:10][C:11]([N:13]2[C:22]3[C:17](=[CH:18][C:19]([CH2:28][N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][C:30]4=[O:36])=[C:20]([CH:23](OC)[O:24]C)[N:21]=3)[CH2:16][CH2:15][CH2:14]2)=[O:12])=[N:8][CH:9]=1)#[N:3].C([O-])(O)=O.[Na+].CCOC(C)=O>C1COCC1.O.C(Cl)Cl>[C:2]([C:4]1[C:5]([NH:37][CH2:38][CH2:39][O:40][CH3:41])=[CH:6][C:7]([NH:10][C:11]([N:13]2[C:22]3[C:17](=[CH:18][C:19]([CH2:28][N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][C:30]4=[O:36])=[C:20]([CH:23]=[O:24])[N:21]=3)[CH2:16][CH2:15][CH2:14]2)=[O:12])=[N:8][CH:9]=1)#[N:3]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 1180370081,8-Naphthyridine-1(2H)-carboxamide, N-[5-cyano-4-[(2-methoxyethyl)amino]-2-pyridinyl]-7-(dimethoxymethyl)-3,4-dihydro-6-[(4-methyl-2-oxo-1-piperazinyl)methyl]-2×

Product 1

HCID 118036971Roblitinib

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Concentrated hydrochloric acid (0.40 ml) was added to a solution of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 80, 470 mg, 0.808 mmol) in THF (3 ml) and water (1 ml) at room temperature. After stirring for 3 h at room temperature saturated aqueous NaHCO3 was added, the mixture extracted with DCM (3×), the organic layers dried over Na2SO4 and evaporated. The residue was sonicated with EtOAc (6 ml) and pentane (6 ml) and then filtered. The white solid obtained was then dissolved in DCM (6 ml), EtOAc added (3 ml), the solution warmed, sealed and allowed to stand at room temperature for 2 h. Filtration and drying gave the title compound as a white solid.

Workup

  1. additionwas added
  2. extractionthe mixture extracted with DCM (3×)
  3. dry with materialthe organic layers dried over Na2SO4
  4. customevaporated
  5. customThe residue was sonicated with EtOAc (6 ml) and pentane (6 ml)
  6. filtrationfiltered
  7. customThe white solid obtained
  8. temperaturethe solution warmed
  9. customsealed
  10. filtrationFiltration
  11. customdrying

Sources & evidence

ORD record
ord-a3469e73730c46899b44804877aed616
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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